Aims: Once-monthly oral ibandronate does not maintain stable
reduction in bone resorption, suggesting that some persons
taking the drug may have little reduction in turnover for at least
part of the dosing interval. Because the extent of reduction in
turnover is correlated with clinical efficacy of bisphosphonates,
this may have important clinical consequences. To explore this
question, we examined the proportion of participants who
reached specified threshold levels of resorption marker
reduction.
Methods: Postmenopausal osteoporotic women participated in
a 3-month, randomized, double-blind, placebo-controlled clinical
trial. Enrolled participants were randomized to receive ibandronate
150 mg or 100 mg or matching placebo every 4 weeks for 3
doses. Serum CTx was measured just prior to each dose, one week
after each dose, and weekly for 4 weeks after the final dose.
Geometric mean percent change from baseline was calculated, as
was the proportion of participants who had marker reductions of
at least 40%, 50%, and 60% at each time point after the third dose
(Weeks 9–12).
Results: At each week after dosing a progressively smaller
proportion of women met the defined sCTx reduction thresholds.
Fewer than half of women taking 150 mg of ibandronate had sCTx
reductions of at least 60% at all 4 weeks after the third dose (Weeks
9–12) and fewer than three-quarters (71.9%) of women had
reductions of at least 40% at all four weeks.
Conclusions: With once-monthly dosing of oral ibandronate,
the proportion of women who attain specified reductions in sCTx
declines progressively with time between doses. Because the observed
cyclic changes in bone resorption might affect efficacy, the
possible clinical implications of intermittent dosing deserve further
study.

Aims: Once-monthly oral ibandronate does not maintain stable
reduction in bone resorption, suggesting that some persons
taking the drug may have little reduction in turnover for at least
part of the dosing interval. Because the extent of reduction in
turnover is correlated with clinical efficacy of bisphosphonates,
this may have important clinical consequences. To explore this
question, we examined the proportion of participants who
reached specified threshold levels of resorption marker
reduction.
Methods: Postmenopausal osteoporotic women participated in
a 3-month, randomized, double-blind, placebo-controlled clinical
trial. Enrolled participants were randomized to receive ibandronate
150 mg or 100 mg or matching placebo every 4 weeks for 3
doses. Serum CTx was measured just prior to each dose, one week
after each dose, and weekly for 4 weeks after the final dose.
Geometric mean percent change from baseline was calculated, as
was the proportion of participants who had marker reductions of
at least 40%, 50%, and 60% at each time point after the third dose
(Weeks 9–12).
Results: At each week after dosing a progressively smaller
proportion of women met the defined sCTx reduction thresholds.
Fewer than half of women taking 150 mg of ibandronate had sCTx
reductions of at least 60% at all 4 weeks after the third dose (Weeks
9–12) and fewer than three-quarters (71.9%) of women had
reductions of at least 40% at all four weeks.
Conclusions: With once-monthly dosing of oral ibandronate,
the proportion of women who attain specified reductions in sCTx
declines progressively with time between doses. Because the observed
cyclic changes in bone resorption might affect efficacy, the
possible clinical implications of intermittent dosing deserve further
study.